JP2010189352A - Transdermal absorption promoting agent and external preparation for skin containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a transdermal absorption promoting agent or a transdermal absorption control agent which allows selective and efficient permeation of only a target drug to a target part in the skin and maintaining the actual concentration over a long period of time, and to provide an external preparation for skin prepared by blending the same. <P>SOLUTION: The transdermal absorption promoting agent or the transdermal absorption control agent is made of a sugar-modified linear silicone. The external preparation for skin contains a drug and the transdermal absorption promoting agent or the transdermal absorption control agent made of a sugar-modified linear silicone as active components. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to a percutaneous absorption enhancer or a percutaneous absorption control agent, and a skin external preparation containing the same.

  More specifically, it is specific by selectively promoting or controlling the transdermal absorption of a water-soluble drug that is present in the aqueous phase or in the vicinity of the aqueous phase region in the preparation and has particularly low permeability to the skin. The present invention relates to a percutaneous absorption enhancer or a percutaneous absorption control agent, and a topical skin preparation containing the same, which are intended to efficiently store in a target site in the skin and increase the effective concentration of a water-soluble drug.

As administration methods for medicinal ingredients, oral administration, administration by injection, and the like have been widely performed.
However, in the case of oral administration, there are drawbacks such as insufficient absorption and side effects such as gastrointestinal disorders.
Moreover, although absorption is quick by administration by injection, specialists such as doctors are necessary.

In recent years, in order to improve such side effects and drawbacks, external preparations by transdermal administration have been developed. Transdermal administration has attracted attention for the following reasons 1 to 4.
1: Long-term administration is possible at a controlled rate.
2: Administration is certain.
3: Difficult to undergo metabolism in the liver.
4: Administration can be stopped if necessary.

  In particular, in the case of external preparations such as cosmetics that use the skin as the active site of the medicinal component, the medicinal component can penetrate directly into the skin, and the active agent is not used to increase the passage of the medicinal component of the skin as in the past It is preferable to use a transdermal external preparation that increases the drug concentration at each site of the skin that is the target site.

However, even in such external preparations, a sufficient skin permeation effect is still not obtained and it is difficult to say that it is a satisfactory state.
In other words, the outermost layer of the skin is called the stratum corneum, and has a physiological function as a barrier layer that originally protects against the invasion of foreign substances from the outside of the body. Just adding a medicinal component to the skin does not sufficiently improve the drug concentration in the skin.

In order to improve this, the main methods are to incorporate a low-molecular transdermal absorption accelerator such as a surfactant or oil, or to enhance the occlusion effect on the skin by using a pack or sheet as the dosage form. It is mentioned as a thing.
For example, Patent Document 1 discloses an external preparation for skin utilizing the percutaneous absorption promotion property made of glyceryl-modified silicone.

However, the use of a low molecular weight surfactant or a transdermal absorption enhancer consisting of an oil component disturbs the stratum corneum lipid, has limitations on the formulation, transiently increases the skin permeation amount, but the intradermal target It is difficult to say that it is sufficient for the reason that the effective concentration cannot be maintained because there is no persistence of concentration at the site.
In addition, polymer percutaneous absorption enhancers that have little effect on stratum corneum lipids, especially oily polymer percutaneous absorption enhancers that are insoluble in water, are difficult to interact with drugs in the aqueous phase. It is not suitable for promoting penetration of drugs into the skin.
In addition, packs and seats are restricted in behavior during use.

  Therefore, the skin permeation enhancer itself has no irritation to the skin, and it is a base that can selectively and efficiently promote the permeation of the target drug only to the target site in the skin. Development has been desired.

  From the above viewpoint, as a result of earnest research on the method of measuring the skin penetration amount of a test object simply and accurately, the inventors have permeated the test substance amount permeated into each intradermal site in Patent Document 2. As an index of the amount of the test substance, it was found that the amount of the skin permeation (concentration) of the test substance can be grasped easily and accurately by associating in vitro or in vivo. And using this evaluation method, in patent document 3, the percutaneous absorption promoter which consists of hydrophilic polyglycerin modified silicone which has a polyglycerin group more than triglycerin is invented.

On the other hand, an organosiloxane having a sugar residue at the silicone end is described in Patent Document 4. Patent Document 5 discloses a transdermal absorption enhancer using an organosiloxane having a specific sugar residue at a silicone terminal.
A cosmetic containing a sugar-modified silicone is described in Patent Document 6.

JP-A-9-118636 JP 2003-183117 A JP 2002-71682 A JP-A-5-186596 JP-A-11-92490 Japanese Patent Laid-Open No. 6-145023

  As a result of further research on a base that selectively enhances the permeability into the skin, the inventors of the present invention, particularly regarding a water-soluble drug with low permeability to the skin, It was found that only the water-soluble drug to be permeated selectively and efficiently penetrates the target site in the skin, and that the effective concentration can be maintained for a long time, and the present invention has been completed.

  The present invention relates to a percutaneous absorption enhancer or transcutaneous agent that can selectively and efficiently penetrate only a target drug into a target site in the skin and maintain its effective concentration in the skin for a long time. An object of the present invention is to provide an absorption control agent and an external preparation for skin containing the same.

  That is, the present invention provides a transdermal absorption enhancer or transdermal absorption control agent comprising a sugar-modified linear silicone.

  The present invention also provides the transdermal absorption enhancer or transdermal absorption control agent, wherein the sugar-modified linear silicone has a structure having a sugar-modified group in the silicone side chain.

  Moreover, this invention provides the skin external preparation which contains a chemical | medical agent and said transdermal absorption promoter or percutaneous absorption control agent as an active ingredient.

  Furthermore, the present invention includes a water-soluble external preparation for skin that contains a water-soluble drug and the above-described transdermal absorption enhancer or transdermal absorption control agent as active ingredients, and further contains 80% or more of the aqueous component. An agent is provided.

According to the present invention, there is provided a percutaneous absorption enhancer or a percutaneous absorption control agent capable of selectively and efficiently penetrating only a target drug into a target site in the skin and maintaining an effective concentration for a long time. Can be provided.
Furthermore, the skin external preparation which mix | blended the chemical | medical agent component can provide the skin external preparation with high safety | security and a good feeling of use.
And when the water-soluble chemical | medical agent which is hard to be absorbed by skin is mix | blended with an external preparation for skin, the transdermal absorption promotion effect will become especially excellent.

  Hereinafter, the present invention will be described in detail.

"Transdermal absorption enhancer or transdermal absorption control agent"
The transdermal absorption enhancer or transdermal absorption control agent of the present invention is a raw material component of an external preparation for skin intended to promote or control the transdermal absorption of a specific drug.

"Sugar-modified linear silicone"
The sugar-modified linear silicone used as a percutaneous absorption enhancer or a percutaneous absorption control agent is a known compound, and is described in Patent Document 4 described above. Patent Document 4 describes a silicone containing a sugar-modified group at one end. However, since only a sugar-modified group at one end has a low substitution rate of a sugar residue, it does not become water-soluble as in the following formula (I) having a sugar-modified group in the silicone side chain.
In the present invention, a structure having a sugar-modified group in the side chain of silicone as shown in the following formula (I) is used. In particular, among the silicone compounds of the following formula (I), m = 0, n = 8, and R1 is the same or different substituted or unsubstituted monovalent hydrocarbon group having 1 to 18 carbon atoms. , Methyl group, ethyl group, phenyl group and the like. A specified sugar-modified linear silicone in which R ² is —R ³ —O—G (R 3 is an organic group having 2 to 20 carbon atoms, G is a glycosyl group derived from a monosaccharide, oligosaccharide or polysaccharide) preferable.

  The sugar-modified linear silicone used in the present application has high water solubility and can be mixed with water at an arbitrary concentration. Furthermore, when the sugar-modified linear silicone used in the present invention is blended with an external preparation for skin, the sugar-modified linear silicone exhibits excellent properties such that it feels light when applied to the skin and is less sticky. For this reason, it is particularly preferable as a percutaneous absorption accelerator or a percutaneous absorption control agent which is a cosmetic raw material.

The sugar-modified linear silicone used in the present invention comprises a hydrophobic part containing a polysiloxane part and a hydrophilic part containing a sugar-modified group, and contains a hydrophobic part and a hydrophilic part in the molecule.
When the drug to be absorbed into the skin is water-soluble because the sugar-modified linear silicone is water-soluble, the drug and the percutaneous absorption enhancer are present in the same aqueous phase, thus directly acting on the active ingredient, The effect of the present invention is further exhibited. The polysiloxane part increases the affinity of organopolysiloxanes with sugar residues in the molecule to sebum and stratum corneum lipids, resulting in a decrease in surface tension of the base containing the active ingredient, resulting in a water-soluble active ingredient It helps to penetrate the active ingredient by increasing the affinity between the skin and the stratum corneum.
Therefore, compared with a hydrocarbon-based substance that does not contain a polysiloxane part, the distribution of the active ingredient to the base is low, and it has the effect of increasing the penetration into the skin.
In addition, the sugar residue is not only essential for maintaining water solubility, but also has a high water retention capacity, so it forms a hydrated film with high active ingredient retention on the surface of the stratum corneum, and the active ingredient is applied to the skin. Can be released continuously. As a result, it has a particularly high skin penetration effect with respect to the active ingredients of water-soluble drugs.
Furthermore, since the molecular weight is relatively large, the percutaneous absorption enhancer itself hardly penetrates into the skin, so that it does not disturb the stratum corneum lipid and is highly safe.

  In the present invention, in order to more effectively exert the effect of promoting percutaneous absorption or controlling percutaneous absorption, it is preferable that the base of the external preparation for skin to be mixed with a drug is aqueous or O / W type.

The transdermal absorption enhancer or transdermal absorption control agent of the present invention is suitably blended in cosmetics, and can efficiently and continuously penetrate the skin with a medicinal component (drug).
As the medicinal component (drug), any of water solubility, oil solubility, and amphiphilic property can be applied, but water solubility is particularly preferable.
Therefore, the skin external preparation of the present invention is preferably an aqueous cosmetic, and the content of the aqueous component constituting the aqueous phase is preferably 50% by mass or more, more preferably 70% by mass or more based on the total amount.
In the lotion containing a water-soluble drug, the content of the aqueous component constituting the aqueous phase is preferably 80% by mass or more based on the total amount.

  Examples of the drug absorbed into the skin by the transdermal absorption enhancer or transdermal absorption control agent of the present invention include, for example, whitening agents, antioxidants, moisturizers, vitamins, various amino acids, hair restorers, antibacterial agents, and hormone agents. And pharmaceutical ingredients including enzymes. Particularly preferred is a water-soluble whitening agent. Specific examples are listed below, but water-soluble drugs are preferred.

  Examples of whitening agents include L-ascorbic acid (vitamin C) and derivatives thereof, pantothenic acid derivatives, tranexamic acid and derivatives thereof, salicylic acid derivatives such as potassium 4-methoxysalicylate, resorcin derivatives, other phenol derivatives, placenta extract and plants. Various extracts such as an extract (for example, chamomile extract) are preferred.

As L-ascorbic acid and its derivatives, for example,
L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid-2-sulfate, L-ascorbic acid 2-glucoside or a salt thereof;
L-ascorbic acid monoalkyl esters such as L-ascorbic acid monostearate, L-ascorbic acid monopalmitate, L-ascorbic acid monooleate;
L-ascorbic acid monoesters such as L-ascorbic acid monophosphate and L-ascorbic acid-2-sulfate;
L-ascorbic acid dialkyl esters such as L-ascorbic acid distearate, L-ascorbic acid dipalmitate, L-ascorbic acid dioleate;
L-ascorbic acid diesters such as L-ascorbic acid diphosphate;
L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trialkyl esters such as L-ascorbic acid trioleate;
Ascorbic acid triesters such as L-ascorbic acid triphosphate;
Examples include L-ascorbic acid glucosides such as L-ascorbic acid 2-glucoside.

  Examples of pantothenic acid derivatives include pantothenyl ethyl ether and pantothenyl alcohol.

  Examples of the tranexamic acid derivative include a dimer of tranexamic acid (for example, trans-4- (trans-aminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid), an ester of tranexamic acid and hydroquinone (for example, trans-4 -Aminomethylcyclohexanecarboxylic acid 4'-hydroxyphenyl ester), ester form of tranexamic acid and gentisic acid (for example, 2- (trans-4-aminomethylcyclohexylcarbonyloxy) -5-hydroxybenzoic acid and its salt), tranexam Amides of acids (eg, trans-4-aminomethylcyclohexanecarboxylic acid methylamide and salts thereof, trans-4- (P-methoxybenzoyl) aminomethylcyclohexanecarboxylic acid and salts thereof, Lance guanidino methyl cyclohexane carboxylic acid and its salts).

  Examples of the antioxidant include glycyrrhizin, glycyrrhizinate (eg, dipotassium glycyrrhizinate, ammonium glycyrrhizinate), allantoin, thiotaurine, glutathione, catechin, albumin, ferritin, and metallothionein.

  Examples of the humectant include urea, glycerin, xylitol, and erythritol.

Examples of vitamins include vitamin A and its derivatives; vitamin B _6, vitamin B ₆ derivatives such as vitamin B ₆ hydrochloride; nicotinic acid, nicotinic acid derivatives of nicotinic acid amide; vitamin E and derivatives thereof; beta-carotene, etc. Is mentioned. In particular, water-soluble vitamins or hydrophilized vitamin derivatives are preferred instead of oil-soluble vitamins (vitamin A and vitamin E).

  Examples of amino acids include hydroxyproline, l-serine, trimethylglycine, and l-arginine.

  Examples of the hair restoring agent include pantothenyl ethyl ether, adenosine, β-glycyrrhetinic acid, and minoxidil.

  Examples of the antibacterial agent include resorcin, sulfur and salicylic acid.

  Examples of the hormonal agent include oxytocin, corticotropin, vasopressin, secretin, gastrin, calcitonin, hinokitiol, and ethinyl estradiol.

  Examples of the enzyme include trypsin, lysozyme chloride, chymotrypsin, semi-alkaline proteinase, serrapeptase, lipase, and hyaluronidase.

  Also, refreshing agents such as camphor and menthol can be used as the water-soluble drug of the present invention.

The sugar-modified linear silicone used in the present invention has a great effect of promoting percutaneous absorption or control of water-soluble drugs.
As the water-soluble drug, a water-soluble drug having a water / octanol partition coefficient log P value of 1.2 or less is particularly preferable.

The LogP value is a coefficient representing polarity according to the ease of distribution of substances into water and octanol as defined in Chemical Reviews vol 71 (6), 525 (1971).
In the present invention, the log P value of 1.2 or less means that the pH value in the external preparation for skin is 1.2 or less.
The log P value of the drug can be calculated with calculation software (PALAAS: manufactured by CompDrug Chemistry Ltd.).

“A water-soluble drug having a logP value of 1.2 or less” becomes less compatible with the stratum corneum, which is a hydrophobic surface, as the logP value becomes smaller (that is, the negative value becomes larger), and becomes less likely to penetrate into the skin. It is known. The aqueous phase, which is a penetrating medium for the “water-soluble drug having a log P value of 1.2 or less”, has poor affinity with the hydrophobic stratum corneum, and therefore has poor wetting on the stratum corneum surface. Therefore, the penetration area into the skin is reduced.
Since the percutaneous absorption amount is proportional to the permeation area between the base and the skin, the permeation amount is reduced when the permeation area is small.

  The present invention provides wettability between the aqueous phase and the skin by allowing hydrophilic sugar-modified linear silicone to coexist in the aqueous phase in which the “water-soluble drug having a log P value of 1.2 or less” exists. Is an epoch-making technique that greatly enhances skin permeability, that is, percutaneous absorption, of a “water-soluble drug having a log P value of 1.2 or less” that is normally difficult to penetrate into the skin.

ｐＨ４〜８の領域での分配係数である（＊１はｐＨ５〜８の範囲）。 “Table 1” exemplifies typical water-soluble drugs having a log P value of 1.2 or less.

This is a partition coefficient in a pH range of 4 to 8 (* 1 is a range of pH 5 to 8).

In the case of an ionic drug, the degree of dissociation varies depending on the pH of the external preparation for skin, so the log P value is a value having a certain range. For example, in the case of tranexamic acid, there are two pKa around pH 4-5 and around pH 10-11, and the dissociation state of the ionic group changes with this pKa as a boundary. At pH where the ratio of ion-dissociated groups is large, the water-soluble ratio increases and the log P value, that is, the value of “log (octanol-water) partition” decreases.
Therefore, the value is -2.87 to -2.49. The “water-soluble drug having a log P value of 1.2 or less” as used in the present invention means that, for an ionic drug such as tranexamic acid, the log P value that can be taken at pH in the preparation is 1.2 or less. It means that it is a water-soluble drug.

The amount of the transdermal absorption enhancer or transdermal absorption control agent of the present invention and the drug incorporated into the external preparation for skin is appropriately determined depending on the type of drug and the intended absorption rate.
Usually, the percutaneous absorption enhancer or the transdermal absorption control agent is blended in an amount of about 0.0001 to 50% by mass based on the total amount of the external preparation for skin, and the drug is blended in an amount of about 0.0001 to 20% by mass based on the total amount of the external preparation for skin. .
Since the external preparation for skin of the present invention is excellent in transdermal absorbability, the amount of the drug can be reduced.
In the present invention, the percutaneous absorption enhancer or the transdermal absorption control agent refers to an external application for skin that has an action of promoting the absorption of a drug (medicinal ingredient) acting on the skin or controlling the absorption rate. It means the raw material of the agent.

  The external preparation for skin of the present invention includes, in addition to the above-mentioned essential components, other components usually used in external preparations for skin, such as powder components, liquid oils, solid oils, waxes, hydrocarbon oils, higher fatty acids, higher alcohols. , Ester oil, silicone oil, anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, thickener, film agent, UV absorber, sequestering agent, lower alcohol, polyhydric alcohol , Sugars, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, antioxidants, antioxidant assistants, fragrances, water, etc. Can be produced in accordance with conventional methods.

  Next, an Example is given and this invention is demonstrated. The present invention is not limited to these examples. Unless otherwise specified, the blending amount represents mass%.

〔一般式（II）中、Ｒ１は同種または異種の炭素数１〜１８の置換または非置換一価炭化水素基を示す。Ｒ⁴は水素原子を示す。ｍおよびｎの平均値は同一または異なった０または正数を示し、かつ1≦ｍ＋ｎ≦１００である〕で表されるオルガノハイドロジェンシロキサンと、一般式（III）で表される糖誘導体とを、白金触媒の存在下にて反応させて、目的の糖変性直鎖状シリコーンを製造することができる。
［化３］
Ｒ⁵−Ｏ−Ｇ （III）
〔式中Ｒ⁵は、分子内に二重結合を有する炭素数1〜１０の炭化水素基を示し、Ｇは、単糖、オリゴ糖又は多糖から誘導されるグリコシル基を示す。〕

なお、反応終了後Siに結合した水素原子が残っている場合には、反応終了後にオレフィン化合物を加え、未反応の水素原子をできるだけ反応させておくことが好ましい。特に式（I）で表される糖変性直鎖状シリコーンのうち、ｍが０〜５、ｎが５〜７０のものは水に溶解し、本発明に関わる親水性薬剤の皮膚浸透効果を得るのに好適である。 "Example 1"
The percutaneous absorption enhancer (or transdermal absorption control agent) used in Example 1 is not particularly limited in the production method of the compound of formula (I), but generally well-known organohydrogenpolysiloxane and terminal are used. It can be produced by a hydrosilyl reaction with a sugar derivative having a double bond.
That is, a sugar-modified linear silicone produced by the following procedure was used.
Formula (II)

[In General Formula (II), R1 represents the same or different substituted or unsubstituted monovalent hydrocarbon group having 1 to 18 carbon atoms. R ⁴ represents a hydrogen atom. an average value of m and n represents the same or different 0 or a positive number, and 1 ≦ m + n ≦ 100], and a sugar derivative represented by the general formula (III) The desired sugar-modified linear silicone can be produced by reacting in the presence of a platinum catalyst.
[Chemical formula 3]
R ⁵ —OG (III)
[Wherein R ⁵ represents a C 1-10 hydrocarbon group having a double bond in the molecule, and G represents a glycosyl group derived from a monosaccharide, oligosaccharide or polysaccharide. ]

In addition, when the hydrogen atom couple | bonded with Si remains after completion | finish of reaction, it is preferable to add an olefin compound after completion | finish of reaction and to make an unreacted hydrogen atom react as much as possible. In particular, among the sugar-modified linear silicones represented by the formula (I), those having m of 0 to 5 and n of 5 to 70 are dissolved in water to obtain the skin penetration effect of the hydrophilic drug according to the present invention. It is suitable for.

“Comparative Example 1”
The water-soluble organopolysiloxane used in Comparative Example 1 is a known EO-modified silicone represented by the following formula.

“Percutaneous absorption promotion effect”
Using the sugar-modified linear silicone of Example 1, the skin permeability promoting effect of various drugs was evaluated by the following evaluation test. The results are shown in “Table 2”.

<Evaluation test>
The evaluation test was performed in an in vitro form. Minipig skin was used as the skin model, and evaluation was carried out by the method described in JP-A-2002-71682 developed by the present inventors.
That is, a simple solution of each drug (an aqueous solution adjusted to pH 6 containing 1% by mass of a water-soluble drug component) or 1% by mass of the above-described solution containing the silicone of Example 1 or Comparative Example 1 is applied to minipig skin. It was applied, incubated at 37 ° C. for 6 hr, the epidermis was extracted with a solvent, and the amount of the drug contained per unit mass was quantified by LC-MASS, thereby comparing the amount of drug permeated into the skin.
LC-MASS used for the measurement is product name 1100Series LC / MSD, manufactured by Agilent.

From the results of “Table 2”, the incorporation of sugar-modified linear silicone (Example 1) improves the penetration and storage properties of various drugs into the skin, and has a particularly remarkable percutaneous absorption effect. Was confirmed.
On the other hand, in the polyoxyalkylene group-containing silicone (water-soluble EO-modified organopolysiloxane) (Comparative Example 1) having no sugar-modified group in the molecule, the percutaneous absorption effect of the medicinal component was not observed.
In addition, by adding sugar-modified linear silicone, the amount of penetration into the skin of preservatives (methylparaben, phenoxyethanol: a drug whose logP value is not less than 1.2) that is an unnecessary component in the skin is From the fact that it was not observed, it was shown that sugar-modified linear silicone has controllability of drug percutaneous absorption.
That is, the present invention has an effect of promoting percutaneous absorption of a drug that is preferably absorbed into the skin, and at the same time, has an effect of controlling percutaneous absorption for preventing absorption of a drug or a component that does not require skin absorption into the skin. Have.

Examples of external preparations for skin (particularly cosmetics) containing the percutaneous absorption enhancer or transdermal absorption control agent of the present invention are shown below.
The following external preparation for skin is an external preparation for skin containing an agent and the transdermal absorption enhancer or transdermal absorption control agent of the present invention having the above-mentioned effects as active ingredients.

"Transparent lotion"
(Mixed component) Compounding amount (% by mass)
1,3-butylene glycol 6
Glycerin 4
Polyoxyethylene / polyoxyalkylene copolymer 5
Oleyl alcohol 0.1
Sugar-modified linear silicone (Example 1) 0.5
Ethanol 10
Arbutin 2
4 Potassium methoxysalicylate 1
Iron oxide 0.001
Phenoxyethanol 1
Citric acid 0.05
Sodium citrate 0.6
Perfume Appropriate amount of purified water Residue (Production method)
Dissolve 1,3-butylene glycol, glycerin, sugar-modified linear silicone, arbutin, and buffer in purified water to obtain an aqueous phase. On the other hand, oleyl alcohol, surfactant, fragrance, colorant and preservative are dissolved in ethanol to form an ethanol phase. This ethanol phase is added to the aqueous phase and solubilized to obtain a transparent lotion.

"Lotion"
(Mixed component) Compounding amount (% by mass)
Dipropylene glycol 1
Sorbit 1
POE (20) oleyl alcohol ether 1
Sugar-modified linear silicone (Example 1) 0.2
Ascorbic acid 2-glucoside 2
Ethanol 15
Phenoxyethanol 0.3
Citric acid 0.05
Sodium citrate 0.6
Iron oxide 0.001
Perfume Appropriate amount of purified water Residue (Production method)
Dipropylene glycol, sorbit, sugar-modified linear silicone, ascorbic acid 2-glucoside, and a buffering agent are dissolved in purified water to obtain an aqueous phase. On the other hand, POE (20) oleyl alcohol ether, fragrance, colorant and preservative are dissolved in ethanol to form an ethanol phase. This ethanol phase is added to the aqueous phase and solubilized to obtain a skin lotion.

"Lotion"
(Mixed component) Compounding amount (% by mass)
Ethanol 10
Dipropylene glycol 1
Sugar-modified linear silicone (Example 1) 1
Polyethylene glycol 1000 1
Polyoxyethylene methyl glucoside 1
Glyceryl tri-2-ethylhexanoate 0.1
Polyoxyethylene (60) hydrogenated castor oil 0.2
Polyglyceryl diisostearate 0.15
N-stearoyl-L-glutamate sodium 0.1
Citric acid 0.04
Sodium citrate 0.18
Potassium hydroxide 0.4
Dipotassium glycyrrhizinate 0.1
Tranexamic acid 2
Arginine 0.1
L-ascorbic acid 2-glucoside 2
Ogon Extract 0.1
Yukinoshita extract 0.1
Phenoxyethanol 0.2
Edetate trisodium 0.05
2-methoxyhexyl paramethoxycinnamate 1.0
Perfume Appropriate amount of purified water Residue (Production method)
A moisturizer and alkali are added to purified water, and then sugar-modified linear silicone, ascorbic acid 2-glucoside, dipotassium glycyrrhizinate, and a buffer are added to obtain an aqueous phase. On the other hand, an oil-soluble component, a fragrance, and a preservative are dissolved in ethanol to form an ethanol phase. This ethanol phase is added to the aqueous phase and solubilized to obtain a skin lotion.

"Lotion"
(Mixed component) Compounding amount (% by mass)
Ethanol 40
Glycerin 38
Dipropylene glycol 8
Erythritol 0.3
Sugar-modified linear silicone (Example 1) 10
Polyethylene glycol 1000 4
Polyoxyethylene methyl glucoside 8
Isostearic acid 0.5
Glyceryl tri-2-ethylhexanoate 4
Polyoxyethylene (60) hydrogenated castor oil 0.7
Polyglyceryl diisostearate 2
Lauryldimethylaminoacetic acid betaine 0.5
Citric acid 0.06
Sodium citrate 0.5
Potassium hydroxide 0.7
Dipotassium glycyrrhizinate 0.5
Trimethylglycine 3
Hipotaurine 0.5
Oil-soluble licorice extract 0.5
L-ascorbic acid 2-glucoside 2
L-Menthol 1
Phenoxyethanol 0.5
Ethylenediamine hydroxyethyl triacetate trisodium 0.1
Edetic acid trisodium 0.2
2-methoxyhexyl paramethoxycinnamate 7
Perfume Appropriate amount of purified water
A moisturizer and alkali are added to purified water, and then sugar-modified linear silicone, ascorbic acid 2-glucoside, dipotassium glycyrrhizinate, and a buffer are added to obtain an aqueous phase. On the other hand, an oil-soluble component, a fragrance, and a preservative are dissolved in ethanol to form an ethanol phase. This ethanol phase is added to the aqueous phase and solubilized to obtain a skin lotion.

"Two-layer lotion"
(Mixed component) Compounding amount (% by mass)
Squalane 8
Sugar-modified linear silicone (Example 1) 0.2
Sorbit 1
Glycerin 1
POE sorbitan tetraoleate 0.2
Ethanol 10
Glutathione 0.2
Hinokitiol 0.1
Phenoxyethanol 0.3
P-Hydroxybenzoate ester 0.12
Iron oxide 0.001
Orange oil 0.01
Purified water residue (production method)
Add POE sorbitan tetraoleate, preservative, colorant, and ethanol to hinokitiol to make an oil phase. The remaining ingredients are mixed to form an aqueous phase. An oil phase and an aqueous phase are mixed to obtain a two-layer lotion.

"Emollient lotion (O / W)"
(Mixed component) Compounding amount (% by mass)
Stearic acid 2
Cetyl alcohol 1.5
Vaseline 2
Squalane 3
Arbutin 3
Retinol 0.5
Tranexamic acid 2
Yukinoshita Extract 0.5
Chamomile extract 0.1
Agar 0.5
Sugar-modified linear silicone (Example 1) 0.5
Sorbitan monooleate 2
Dipropylene glycol 5
Polyoxyethylene / polyoxyalkylene copolymer 2
Polyethylene glycol (PEG1500) 3
L-glutamic acid 0.3
Triethanolamine 0.05
Citric acid 0.05
Sodium citrate 0.6
Phenoxyethanol 0.3
P-Hydroxybenzoate ester 0.12
Perfume Appropriate amount of purified water Residue (Production method)
A moisturizer and alkali are added to purified water, and then L-glutamic acid and a buffer are added to form an aqueous phase. An oil-soluble component is dissolved in an oil, and this is mixed with an aqueous phase and emulsified with a homomixer to obtain an O / W type emollient lotion.

"Emollient lotion (O / W)"
(Mixed component) Compounding amount (% by mass)
Vaseline 2
Methyl polysiloxane 2
Sugar-modified linear silicone (Example 1) 0.5
Ethanol 5
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7
1,3-butylene glycol 5
Polyethylene glycol 20000 0.5
Jojoba oil 3
Squalane 2
Cholesteryl hydroxystearate 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 1
Polyoxyethylene (60) hydrogenated castor oil 1
Potassium hydroxide 0.1
Sodium pyrosulfite 0.02
Sodium metaphosphate 0.05
Stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
Arbutin 7
L-serine 1
DL-α-tocopherol acetate 0.1
Sodium hyaluronate 0.05
Paraoxybenzoic acid ester 0.1
Edetate trisodium 0.05
4-t-butyl-4′-methoxydibenzoylmethane 0.5
Diparamethoxycinnamate mono-2-ethylhexylate glyceryl
0.5
Xanthan gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue (production method)
A moisturizer, surfactant, sugar-modified linear silicone, drug and chelating agent are added to purified water to dissolve the carboxyvinyl polymer. The remaining components are mixed and dissolved, and emulsified with a homomixer at 70 ° C. to obtain an O / W type emollient lotion.

"Lotion (O / W)"
(Mixed component) Compounding amount (% by mass)
Stearyl alcohol 0.5
Vitamin E acetate 1
Tranexamic acid 5
Hardened palm oil 2
Liquid paraffin 3
Sugar-modified linear silicone (Example 1) 1
Polyoxyethylene-modified silicone 0.1
Dipropylene glycol 6
Polyethylene glycol (PEG400) 4
Sorbitan sesquioleate 1.6
Carboxyvinyl polymer 1.5
Potassium hydroxide 0.42
Phenoxyethanol 0.3
Edetate trisodium 0.1
Perfume Appropriate amount of purified water Residue (Production method)
Add humectant, surfactant, drug, chelating agent to purified water and dissolve carboxyvinyl polymer. The remaining components are mixed and dissolved, and emulsified with a homomixer at 70 ° C. to obtain an O / W type lotion.

"Emollient lotion (W / O)"
(Mixed component) Compounding amount (% by mass)
Microcrystalline wax 1
Beeswax 2
Lanolin 2
Liquid paraffin 10
Squalane 20
Vitamin A palmitate 2
Potassium 4-methoxysalicylate 2
Sugar-modified linear silicone (Example 1) 0.5
Propylene glycol 7
Sorbitan sesquioleate 4
POE (20) sorbitan monooleate 1
Phenoxyethanol 0.3
Magnesium ascorbate phosphate 2
Glycine 0.5
Erythritol 0.5
Citric acid 0.05
Sodium citrate 0.6
Orange oil 0.01
Purified water residue (production method)
A water-soluble component is added and dissolved in purified water to obtain an aqueous phase. An oil component, an oil-soluble component, and a surfactant are mixed and dissolved at 70 ° C. and emulsified with a homomixer while gradually adding the previous aqueous phase thereto to obtain a W / O type emollient lotion.

"Cream (O / W)"
(Mixed component) Compounding amount (% by mass)
Methyl polysiloxane 2
Decamethylcyclopentasiloxane 28
Behenyl alcohol 0.77
Batyl alcohol 1.65
Sugar-modified linear silicone (Example 1) 5
Glycerin 4
Dipropylene glycol 5
Lavender oil 0.04
White beeswax 1.65
Glyceryl tri-2-ethylhexanoate 1
Cetyl 2-ethylhexanoate 1
Citric acid 0.01
Sodium citrate 0.09
Potassium hydroxide 0.42
Dipotassium glycyrrhizinate 0.05
Trimethylglycine 0.1
L-ascorbic acid 2-glucoside 2
DL-α-tocopherol acetate 0.1
P-Hydroxybenzoate ester 0.12
Dibutylhydroxytoluene 0.01
Edetate trisodium 0.1
Purified water residue (production method)
A moisturizer, surfactant, sugar-modified linear silicone, drug and buffer are added to purified water and dissolved. The remaining components are mixed and dissolved, and emulsified with a homomixer at 70 ° C. to obtain an O / W type cream.

"Emollient cream (W / O)"
(Mixed component) Compounding amount (% by mass)
Squalane 15
Decamethylcyclopentasiloxane 5
Cetyl isooctanoate 8.5
Ascorbic acid dipalmitate 2
Microcrystalline wax 1
Sugar-modified linear silicone (Example 1) 0.2
Organically modified smectite 1.3
POE glycerol triisostearate 0.2
Cyclodextrin 0.2
Glycerin 10
Phenoxyethanol 0.3
P-Hydroxybenzoate ester 0.2
Perfume Appropriate amount of purified water Residue (Production method)
Add clay minerals, surfactants, preservatives, and fragrances to the oil and uniformly disperse, and then add chemicals to obtain an oily gel. A moisturizer and other water-soluble components are added to purified water, dissolved, added to the previous oil phase, and stirred with a homomixer to obtain a W / O type emollient cream.

"Oil-based gel"
(Mixed component) Compounding amount (% by mass)
Liquid paraffin 6
Polydimethylsiloxane 6
Glycerol tri-2 ethylhexanoate 50
Sorbitol 10
Polyethylene glycol (PEG400) 5
Acylmethyl taurine 5
POE octyldodecyl alcohol ether 10
Sugar-modified linear silicone (Example 1) 0.5
Vitamin A palmitate 2
Resorcin derivative 0.5
Lavender oil 0.001
Purified water residue (production method)
Add humectant and acylmethyl taurine to purified water to make water phase. The remaining components are mixed and dissolved to form an oil phase, which is added to the previous aqueous phase with stirring with a homomixer and emulsified to obtain an oily gel.

"Moisture Gel"
(Mixed component) Compounding amount (% by mass)
Dipropylene glycol 7
Polyethylene glycol (PEG400) 8
Carboxyvinyl polymer 0.4
Methylcellulose 0.2
POE (15) oleyl alcohol ether 1
Potassium hydroxide 0.1
Sugar-modified linear silicone (Example 1) 0.5
Ascorbic acid 3
Urea 10
Phenoxyethanol 0.3
Citric acid 0.05
Sodium citrate 0.6
Perfume Appropriate amount of purified water Residue (Production method)
After water-soluble polymer is uniformly dissolved in purified water, the remaining components are added and uniformly dissolved to obtain a moisture gel.

"Moisture Gel"
(Mixed component) Compounding amount (% by mass)
Polyoxyethylene / methylpolysiloxane copolymer 5
Sugar-modified linear silicone (Example 1) 1
Dipropylene glycol 3
Erythritol 1
1,3-butylene glycol 10
Polyethylene glycol 1500 1
Polyoxyethylene methyl glucoside 1
Polyethylene glycol diisostearate 5
Dipotassium glycyrrhizinate 0.5
Resorcin derivative 0.5
P-Hydroxybenzoate ester 0.2
Edetic acid-3 sodium 0.01
Hydroxypropyl methylcellulose 0.7
Carboxyvinyl polymer potassium 0.5
Purified water residue (production method)
After water-soluble polymer is uniformly dissolved in purified water, the remaining components are added and uniformly dissolved to obtain a moisture gel.

"Emollient cream (W / O)"
(Mixed component) Compounding amount (% by mass)
Squalane 15
Decamethylcyclopentasiloxane 5
Cetyl isooctanoate 8.5
Ascorbic acid dipalmitate 2
Potassium 4-methoxysalicylate 2
Microcrystalline wax 1
Sugar-modified linear silicone (Example 1) 0.2
Organically modified smectite 1.3
POE glycerol triisostearate 0.2
Glycerin 10
Phenoxyethanol 0.3
Perfume Appropriate amount of purified water Residue (Production method)
Add clay minerals, surfactants, preservatives, and fragrances to the oil and uniformly disperse, and then add chemicals to obtain an oily gel. A moisturizer and other water-soluble components are added to purified water, dissolved, added to the previous oil phase, and stirred with a homomixer to obtain a W / O type emollient cream.

"Emollient lotion (O / W)"
(Mixed component) Compounding amount (% by mass)
Stearic acid 2
Cetyl alcohol 1.5
Vaseline 4
Squalane 5
Retinol 0.8
Sugar-modified linear silicone (Example 1) 0.5
Sorbitan monooleate 2
Dipropylene glycol 5
Polyethylene glycol (1500) 3
L-glutamic acid Na 0.3
Triethanolamine 0.1
Phenoxyethanol 0.3
Potassium 4-methoxysalicylate 1
Citric acid 0.01
Sodium citrate 0.09
Perfume Appropriate amount of purified water Residue (Production method)
A moisturizer and alkali are added to purified water, and then L-glutamic acid and a buffer are added. An oil-soluble component is dissolved in an oil, and emulsified with a water phase and a homomixer to obtain an O / W type emollient lotion.

"mask"
(Mixed component) Compounding amount (% by mass)
Vaseline 6
Behenyl alcohol 2.5
Glycerin 9
Maltitol solution 2
Polyethylene glycol 1500 12
Sugar-modified linear silicone (Synthesis Example 1) 0.1
Squalane 11
Potassium behenate 2
Cholesteryl hydroxystearate 0.1
N-alkylene (20-30) glycol monoisostearate 3
Cetyl 2-ethylhexanoate 4
Polyoxyethylene (60) hydrogenated castor oil 0.3
Self-emulsifying glyceryl monostearate 2
Titanium oxide 1
Sodium metaphosphate 0.1
L-Arginine 0.1
Vitamin E acetate 0.1
Carrot extract 0.1
P-Hydroxybenzoate ester 0.3
Bentonite 0.5
Purified water Residual fragrance Appropriate amount (Manufacturing method)
Titanium oxide, glycerin, maltitol aqueous solution, polyethylene glycol 15000, sugar-modified cyclic silicone and carrot extract are added to purified water and mixed thoroughly. The remaining water-soluble components are added to this mixed solution and stirred to obtain an aqueous phase. Vaseline and behenyl alcohol are mixed with squalane, the remaining oil-soluble components are added to this, and the mixture is stirred and further emulsified with an aqueous phase and a homomixer to obtain a rinse-type mask.

"lipstick"
(Mixed component) Compounding amount (% by mass)
Titanium dioxide 4.5
Red No. 201 0.5
Red No. 202 2
Red 223 0.05
Ceresin 4
Candelilla Row 8
Carnavalou 2
Castor oil 25
Isostearic acid diglyceride 40
POE (25) polyoxypropylene (20) 2-tetradecyl ether 1
Retinol 1
Glycerin 2
Propylene glycol 1
Sugar-modified cyclic silicone (Synthesis Example 1) 0.5
Octyl methoxycinnamate 0.01
α-Tocopherol 0.1
Purified water residue (production method)
Titanium dioxide, red No. 201 and No. 202 are added to a part of castor oil and treated with a roller. Red No. 223 is dissolved in castor oil. Purified water, glycerin and propylene glycol are uniformly dissolved at 80 ° C. Mix other ingredients, add pigment part and dye part, disperse uniformly with homomixer, add water phase, emulsify with homomixer, pour into mold and cool to obtain lipstick.

"Hair nourishing agent, white hair prevention agent"
(Mixed component) Compounding amount (% by mass)
Pantothenyl ethyl ether 0.5
β-glycyrrhetinic acid 0.5
Assembly extract paste 0.5
Nicotinamide 0.5
Vitamin E acetate 0.5
Salamander extract 0.1
Ethanol 70
Sugar-modified linear silicone (Example 1) 0.5
Isostearyl alcohol 5
Sodium lauryldimethylamine oxide oleate 0.5
Hardened castor oil ethylene oxide (40 mol adduct) 0.5
Purified water residue (production method)
Each component is added to ethanol to obtain an essence for hair care having effects of nourishing hair and preventing white hair.

  According to the present invention, a percutaneous absorption enhancer or a percutaneous absorption control agent capable of selectively and efficiently penetrating only a target drug into a target site in the skin and maintaining an effective concentration for a long time, And the skin external preparation which mix | blended this can be provided.

Claims (4)

  A transdermal absorption enhancer or transdermal absorption control agent comprising a sugar-modified linear silicone.   The transdermal absorption promoter or transdermal absorption control agent according to claim 1, wherein the sugar-modified linear silicone has a structure having a sugar-modified group in a silicone side chain.   An external preparation for skin containing a drug and a transdermal absorption enhancer or transdermal absorption control agent according to claim 1 or 2 as active ingredients.   A water-soluble drug and the percutaneous absorption enhancer or transdermal absorption control agent according to any one of claims 1 to 3 are contained as active ingredients, and the content of the aqueous component is 80% by mass or more based on the total amount. A topical aqueous skin preparation.